1. Field of the Invention
The present invention relates to therapeutic agents for bronchial asthma that effectively suppress asthmatic responses, especially late asthmatic response.
2. Description of the Prior Art
In general, bronchial asthma has been recognized as a disease which is characterized by contraction of smooth muscles in the airway due to type I allergy. However, recent advances in the research of this field have revealed a part of the pathogenesis of asthma, which is characterized by reversal airflow limitation, airway inflammation, mucus hypersecretion and remodeling of the airway structure due to chronic inflammation. Pharmacological therapy should be established beyond understanding of such pathogenesis.
At present available medications for asthma are quick-relievers to reverse airflow limitation such as beta-agonists and xanthine derivatives, and controllers to prevent symptoms by means of suppressing airway inflammation such as corticosteroids inhalants accompanying symptoms like cough, chest tightness and wheezing, while controllers are used daily for a long term basis to suppress persistent inflammation.
However, inhaled corticosteroids as a controller potentiates oropharyngeal candidiasis, dysphonia and occasional coughing from upper-airway irritation in spite that the risk for systemic effects of an inhalant is less than systemic corticosteroids. Moreover, the usage how to inhale steroids is annoying a lot of patients. Long term use of oral or parenteral corticosteroids can cause serious adverse-effects like as osteoporosis, arterial hypertension, diabetes hypothalamic-pituitary-adrenal axis suppression, cataracts, obesity, skin thinning leading to cutancous striae and easy bruisability, and muscle weakness. Controller agents are administered for a long periods, and therefore the systemic side effects of those agents should be avoided or minimized.
From the viewpoint of medical economy, inexpensive asthma-controller medicines have been desired to be developed. Although inhaled corticosteriods are very effective for asthma management, the expensiveness of these drugs has not only a great expense to most of asthmatics but also a burden to national finance of each countries. Nowadays, many patients are probably eager for the development of another type of anti-inflammatory medicines for asthma management instead of inhaled corticosteroids. In such means, a novel and safe anti-asthma medicine has been looked for in this field.
Two kinds of asthmatic responses, i.e., immediate airflow limitation after the antigen challenge and several hours following that, have been recognized to be observed. The early reaction is referred as immediate asthmatic response (IAR) and following phenomenon as late asthmatic response (LAR). IAR has been recognized by airflow limitation which results from acute bronchoconstriction due to allergen exposure, while LAR is due to airway inflammation in the airway. The airway inflammation, which were characterized usually by extensive infiltration of eosinophils, mast cells and mononuclear cells, causes edematous swelling of the airway wall accompanied with or without smooth muscle contraction. Those pathologic changes would be related not only to LAR but also to airway hyperreactivity and aggravating asthma Metzger, W. J. , Hunninghake, G. W. and Richarson, H. B.: Late Asthmatic Responses; Inquiry into Mechanism and Significance, Clin. Rev. Allergy 3:145, 1985). The mechanism of this pathological feature has not been elucidated fully.